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At least 271 records · Page 15Linked to original sources
PubMed1988

Flunarizine inhibits endothelium-dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle.

1. Hypoxia augments contractile responses to several vasoactive agents in canine isolated coronary arteries with intact endothelium. Calcium antagonists inhibit the further increases in tension caused by hypoxia. The present experiments were designed to determine whether the calcium-antagonist flunarizine would inhibit hypoxic contractions in isolated blood vessels through an action on the endothelium or on the vascular smooth muscle. 2. Rings of canine coronary arteries, with or without endothelium, were suspended at optimal length for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. 3. Hypoxia (95% N2 and 5% CO2) augmented contractile responses to prostaglandin F2 alpha (2 x 10(-6) M); removal of the endothelium abolished this hypoxic facilitation. 4. Flunarizine (5 x 10(-5)-5 x 10(-7) M) exerted a long-lasting inhibition of the hypoxic facilitation in a concentration-dependent manner. Flunarizine did not inhibit the response to prostaglandin F2 alpha. 5. To differentiate between the response of smooth muscle and the endothelium, strips of coronary arteries without endothelium were layered with strips with or without endothelium. Hypoxia augmented contractions only in layered preparations with endothelium. Flunarizine prevented the hypoxic contractions in layered preparations in which only the smooth muscle was treated with flunarizine. In contrast, when only the endothelium was treated, no or minimal inhibition of the hypoxic contraction occurred with flunarizine (10(-5) and 5 x 10(-5) M, respectively). 6. These experiments indicate that the calcium antagonist flunarizine inhibits endothelium-dependent hypoxic facilitation in canine coronary arteries primarily through its action on vascular smooth muscle.

Animals↗
PubMed1991

Comparison of endothelium-dependent responses of monkey cerebral and temporal arteries.

1. Endothelium-dependency of vasodilator responses was compared in helical strips of monkey cerebral and superficial temporal arteries contracted with prostaglandin F2 alpha. Acetylcholine produced an endothelium-dependent relaxation in the temporal arteries, but did not consistently alter the tone of cerebral arteries. 2. Adenosine 5'-triphosphate (ATP) produced a transient contraction followed by a relaxation in the temporal and cerebral arteries; removal of the endothelium partially attenuated the relaxation of the cerebral arteries and markedly suppressed the relaxation in the temporal arteries. The dependency of adenosine 5'-diphosphate (ADP)-induced relaxations on the endothelium was also greater in temporal arteries than in cerebral arteries. 3. Histamine-induced relaxations in the temporal arteries were independent of the endothelium and were reversed to contractions by cimetidine. Cerebral arterial relaxations induced by histamine were partly dependent on the endothelium. Relaxations caused by substance P were reversed to contractions by removal of the endothelium in the temporal arteries, whereas the peptide did not consistently alter the tone of cerebral arteries. 4. The Ca2+ ionophore, A23187, relaxed the temporal and cerebral arteries to a similar extent; removal of the endothelium abolished these relaxations. Glyceryl trinitrate elicited similar relaxation of cerebral and temporal arteries, and these were independent of the endothelium. 5. These findings clearly indicate heterogeneity in the endothelium-dependency of several vasodilator responses in monkey intra- and extracranial arteries, although the ability of these arteries to respond to A23187 and glyceryl trinitrate does not appear to differ. The heterogeneous responses observed so far could therefore be due to different distributions of receptors or to variation in receptor-effector coupling in endothelial cells.

Acetylcholine↗
PubMed1993

Acetylcholine-induced endothelium-independent relaxations in monkey isolated superior and inferior caval veins.

1. We examined the effects of acetylcholine (ACh), isoprenaline (Isop) and Ca-ionophore, A23187 on monkey isolated superior (SCV) and inferior caval veins (ICV) with and without intact endothelium, which had been partially contracted by 2 x 10(-6)-5 x 10(-6) M prostaglandin F2 alpha (PGF2 alpha). 2. Low concentrations of ACh (10(-10)-10(-9) M) produced a dose-dependent relaxation in the precontracted venous segments with endothelium. ACh at concentrations more than 10(-7) M elicited a transient contraction followed by a relaxation in these segments. 3. An addition of 5 x 10(-7) M A 23187 induced about 60% of maximum relaxation produced by 10(-5) M sodium nitroprusside (SNP) in each venous segment with endothelium. 4. Isop (10(-10)-10(-5) M) caused a dose-related relaxation in the precontracted caval veins with intact endothelium. 5. Removal of endothelium caused no significant effect on the ACh-induced dual responses but a significant inhibition of the A23187-induced relaxation. 6. Pretreatment with atropine antagonized competitively the ACh-induced relaxations in the endothelium-intact and endothelium-denuded caval veins. The Schild plot analysis showed that the pA2 values of the segments with and without endothelium were 9.72 +/- 0.14 (n = 5) and 10.01 +/- 0.23 (n = 6) in the ICV; and 9.95 +/- 0.20 (n = 5) and 9.70 +/- 0.10 (n = 5) in the SCV, respectively. 7. Pretreatment with 5 x 10-5M aspirin, 3 x 10-5M N0-nitro-L-arginine methylester, 1 mM tetraethylammonium,or 3 x 10-6 M glibenclamide caused no significant effect on the basal tone, ACh induced transient contraction, and ACh;.induced relaxation in the precontracted venous segments with and without endothelium.8. Pretreatment with 10-5 M methylene blue produced a significant reduction of the ACh- and SNP induced relaxations in the precontracted venous segments with and without endothelium. The pretreatment with the same concentration of methylene blue, however, caused no significant effect on the Isop-induced relaxation in venous segments with endothelium.9. The results suggest that ACh acts directly on the venous smooth muscle cells via a high-affinity muscarinic receptor subtype to accumulate cellular cyclic GMP producing endothelium-independent relaxation in the monkey caval veins.

Acetylcholine↗
PubMed1994

Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.

1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT. 7. These results indicate that 5-HT-induced contraction in basilar arteries is substantially attenuated by an endothelium-dependent mechanism in WKY, but to a much lesser extent in SHR. The major relaxing factor released by 5-HT from endothelium in WKY is distinct from NO and may exert its effect by activating K+ channels.

Animals↗
PubMed1995

Evidence that nitric oxide from the endothelium attenuates inherent tone in isolated pulmonary arteries from rats with hypoxic pulmonary hypertension.

1. The inherent contractile tone, and its modulation by the endothelium, have been studied in isolated pulmonary artery preparations taken from rats in which pulmonary hypertension was induced by exposure to a hypoxic environment (10% O2) for 14 days. Control rats were housed in room air. 2. All preparations in which the endothelium was left intact relaxed in response to acetylcholine (43 +/- 4% and 54 +/- 9%, reversal of the noradrenaline-induced contraction in control and hypoxic rats, respectively) indicating that the endothelium was functional in both groups of rats. 3. Exposure of the preparations to Ca(2+)-free physiological salt solution containing 2 mM EGTA for 30-40 min had no effect on preparations from control rats but caused relaxation in preparations from hypoxic rats. The relaxation (taken as a measure of the inherent tone in the preparations) was larger in preparations without endothelium (14.5 +/- 1.9 mN mm-2; n = 5) than in preparations with endothelium (9.1 +/- 1.2 mN mm-2; n = 5). 4. In preparations from hypoxic rats the magnitudes of the contractions to 80 mM K+ and to noradrenaline (0.1 microM) were less than in preparations from control rats. This may have been because the preparations from hypoxic rats were already partially contracted due to the inherent tone. 5.The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1-1 100 microM)had negligible effect on preparations from control rats or on endothelium-denuded preparations from hypoxic rats, but produced concentration-dependent contractions (maximum contraction 7.4 +/- 0.7 mN mm-2 (n = 4) with 100 micro M) in endothelium-intact preparations from hypoxic rats. This effect of L-NAME was prevented by L-arginine (1 mM) but not by D-arginine (1 mM).6. Contractions to L-NAME were also seen in endothelium-intact arteries from control rats if the preparations were first partially contracted by exposure to K+, endothelin, U46619 (thromboxane mimetic)or noradrenaline.7 It is concluded that isolated pulmonary artery rings from hypoxic rats, but not those from control rats, have substantial inherent tone. This inherent tone is normally attenuated by the generation of an endothelium-derived factor that is probably NO. A stimulus for the release of NO from the endothelium may be the contraction of the underlying smooth muscle, whether the contraction is inherent in the tissue, as in preparations from hypoxic rats, or is induced by a vasoconstrictor spasmogen.

Acetylcholine↗
PubMedDate not supplied

Endothelium-dependent and -independent coronary relaxation induced by urocortin.

Urocortin, a newly identified polypeptide, possesses cardiac effects. However, the underlying mechanism of its coronary action is still unclear. In the present study we investigated the possible role of endothelial nitric oxide and Ba2+-sensitive K+ channels in the endothelium-dependent relaxant response to urocortin in the isolated rat left anterior descending coronary arteries. Changes of vessel tone were measured in microvessel myographs. Urocortin produced both endothelium-dependent and -independent relaxation with IC50 of 2.52 nM and 16.5 nM, respectively. Denuation of endothelium decreased the relaxing potency of urocortin. In the endothelium-intact rings pretreated with 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME) or 10 microM 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1-one (ODQ), the urocortin-induced relaxation was similar to that observed in endothelium-denuded rings. The relaxant response to urocortin was markedly reduced in endothelium-intact rings preconstricted by 35 mM K+. Pretreatment with 100 microM BaCl2 significantly reduced urocortin-induced relaxation without an effect on the maximum relaxation. Combined treatment with BaCl2 plus L-NAME did not produce additive inhibition. In contrast, BaCl2 did not alter urocortin-induced relaxation in the endothelium-denuded rings. In the endothelium-denuded rings, BaCl2 at 100 microM also inhibited nitric oxide donor-induced relaxation. In conclusion, our results suggest that urocortin-induced endothelium-dependent relaxation of rat coronary arteries is primarily mediated by endothelial nitric oxide and subsequent activation of Ba2+-sensitive K+ channels. The urocortin-induced endothelium-dependent relaxation appears to be cyclic GMP-dependent.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Endothelium-independent potentiation by neuropeptide Y of vasoconstrictor responses in isolated arteries from rat and rabbit.

An endothelium-dependent action of neuropeptide Y (NPY) has been implicated in studies on various vascular beds. In the present study, the requirement of an intact endothelium for NPY-evoked potentiation of the response to sympathetic nerve stimulation was determined in the small mesenteric arteries of the rat and in the central ear artery of the rabbit. Further, NPY-mediated inhibition of relaxing influences was determined in small mesenteric arteries of the rat. Vascular segments were mounted in a double myograph, where one of the two suspended vessels was denuded of endothelium by gently rubbing the intimal surface. Removal of endothelium was verified by en-face silver staining. In both species, the response to bursts of transmural field stimulation eliciting 10% of maximal contraction was potentiated 2-4 times in the presence of 10 nM NPY, whether the endothelium was present or not. In small mesenteric arteries precontracted with noradrenaline, addition of acetylcholine (I microM) caused relaxation only in vessels with an intact endothelium. Subsequent addition of 10 nM NPY enhanced vasoconstriction in both intact and endothelium-denuded vessels. The endothelium-independent beta-adrenergic agonist isoprenaline (I microM) relaxed both intact and denuded small mesenteric arteries, and in both further addition of 10 nM NPY increased the contraction to about the same extent. The results demonstrate that NPY potentiates the responses to sympathetic field stimulation in small mesenteric arteries from the rat and in central ear artery from rabbit whether the endothelium is present or not. NPY inhibits both endothelium-dependent and -independent relaxations in small mesenteric arteries from rat.

Animals↗
PubMed1985

Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium.

Experiments were designed to determine the role of the endothelium in the facilitation by anoxia of contractile responses of isolated coronary arteries. Rings and strips of canine coronary arteries, with or without endothelium, were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution. To determine the release of a vasoactive substance(s) from the endothelial cells, strips without endothelium were layered with strips containing endothelium. In rings and in layered preparations with endothelium, anoxia (95% N2-5% CO2) augmented contractile responses to prostaglandin F2 alpha. Hypoxia (10 or 5% O2) caused contractions in the presence of indomethacin. Removal of the endothelium abolished the anoxic facilitation, and the hypoxic contractions. Inhibitors of cyclo-oxygenase, lipoxygenase or phospholipase A2 or of adrenergic, serotonergic and histaminergic receptors did not prevent the response to anoxia. Likewise, inhibitors of the endothelium-derived factor(s) (quinacrine, phenidone and methylene blue) did not affect the anoxic facilitation. Hypoxia and anoxia caused contraction of coronary arteries without endothelium when layered with femoral arteries and veins with endothelium. Anoxic facilitation was observed in femoral arteries, but not in femoral veins, with endothelium. These experiments indicate that hypoxia and anoxia cause the release of a diffusible vasoconstrictor substance(s) from endothelial cells. The sensitivity of smooth muscle of different anatomical origin to the facilitatory mediator(s) varies.

Acetylcholine↗
PubMed1992

Effects of proteins on the permeability of monolayers of cultured bovine arterial endothelium.

1. Monolayers of arterial endothelium on porous membranes were exposed to a pressure of 15 cmH2O at 37 degrees C, or of 30 cmH2O at 0 degree C. At constant pressure, the rate of liquid flow per unit area (Jv/A) through each monolayer decreased with time, in the way previously described for cultured endothelium. This phenomenon has been called sealing. After Jv/A stabilized, the pressure was reduced and the hydraulic permeability (Lp) of the endothelium was calculated from the relationship between Jv/A and pressure. Endothelium was seen to be damaged after some experiments at 37 degrees C, but appeared undamaged after experiments at 0 degree C. 2. Bovine serum albumin (BSA) did not influence the Lp of cultured endothelium. At 37 degrees C, the mean (+/- S.E.M.) endothelial Lp was 47.2 +/- 7.3 x 10(-7) cm s-1 cmH2O-1 (n = 10) in the presence of BSA (5 g (100 ml)-1). This is not significantly different from the mean (+/- S.E.M.) Lp of 53.4 +/- 9.0 x 10(-7) cm s-1 cmH2O-1 (n = 9) in the absence of added protein (P greater than 0.10). At 0 degree C also, there was no significant difference between mean Lps in the presence of BSA (0.1 g (100 ml)-1) and in the absence of added protein. 3. Solutions of BSA (5 g (100 ml)-1 or of the neutral polymer Ficoll 70 (4 g (100 ml)-1) did not exert any effective osmotic pressure across endothelium at 37 or 0 degrees C, respectively. 4. BSA (0.1 g (100 ml)-1) did not enable solutions of Ficoll 70 (4 g (100 ml)-1) to exert an effective osmotic pressure across endothelium at 0 degree C. 5. The mean Lp of endothelium at 0 degree C was significantly lower in the presence of cationized ferritin (CF; 0.1 g (100 ml)-1) than in the absence of added protein (P less than 0.001). Native ferritin (NF; 0.1 g (100 ml)-1) had no effect on Lp. 6. In the presence of CF (0.1 g (100 ml)-1), solutions of Ficoll 70 (4 g (100 ml)-1) exerted a mean effective osmotic pressure of 27.7 cmH2O (n = 5) across endothelium at 0 degree C. The mean effective osmotic pressure exerted across endothelium by solutions of Ficoll 70 (4 g (100 ml)-1) plus NF (0.1 g (100 ml)-1) was 1.2 cmH2O (n = 4).

Animals↗
PubMed1989

The endothelium inhibits activation by calcium of vascular neurotransmission.

The role of calcium in the inhibition by the endothelium of adrenergic neurotransmission was studied in isolated rabbit carotid artery. Contractions induced by transmural electrical field stimulation (0.5-8 Hz), norepinephrine (10(-8)-3 X 10(-5) M), potassium depolarization (15-30 mM), or by readdition of calcium (0.15-2.4 mM) to a calcium-free medium containing potassium (15 mM) were significantly smaller in rings with compared with rings without endothelium. The voltage-dependent calcium channel activator, BAY K 8644 (10(-6) M), increased contractions to all contractile stimuli in rings with more than in rings without endothelium and thereby abolished the inhibitory influence of the endothelium. The inhibition of neurogenic contractions by the endothelium was also, in part, prejunctional, as indicated by decreased overflow of endogenous norepinephrine from superfused segments with compared with segments without endothelium evoked by electrical stimulation (2 Hz) or by reinfusion of calcium (2.5 mM) to calcium-free medium containing potassium (80 mM). BAY K 8644 (10(-6) M) enhanced the overflow of norepinephrine evoked by electrical stimulation or calcium from segments with more than from segments without endothelium and abolished the difference. Thus the endothelium inhibits activation by extracellular calcium of adrenergic nerves and vascular smooth muscle. The action of the endothelium is overcome by BAY K 8644, suggesting that voltage-dependent calcium channels are important in the inhibitory role of the endothelium in both adrenergic nerves and smooth muscle cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Selective production of endothelium-derived nitric oxide in canine femoral veins.

In arteries, analogues of L-arginine inhibit the synthesis of nitric oxide and thereby reduce endothelium-dependent relaxations. Experiments were designed to determine whether analogues of L-arginine affect endothelium-dependent responses in a systemic vein. Rings cut from canine femoral arteries and veins were suspended for the measurement of isometric force in organ chambers. In some rings, the endothelium was deliberately removed. All experiments were conducted in the presence of indomethacin (10(-5) M). NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) reduced significantly endothelium-dependent relaxations to acetylcholine, ADP, and thrombin in arteries but not in veins. In the veins, the alpha 2-adrenergic agonist BHT-920 caused contractions which were reduced in rings with endothelium. L-NMMA eliminated the difference in contraction between rings with and without endothelium in the veins. This effect was reversed by L- but not D-arginine (3 x 10(-4) M). N omega-nitro-L-arginine (10(-4) M) reduced endothelium-dependent relaxations to acetylcholine, thrombin, and the calcium ionophore A23187 in venous rings. However, it did not alter the contractions to BHT-920 in rings with or without endothelium. L-Canavanine did not alter endothelium-dependent relaxations in the veins. These results suggest that synthesis of nitric oxide is associated with stimulation of alpha 2-adrenergic, muscarinic, and thrombin receptors on venous endothelial cells. Furthermore, the analogues of L-arginine affect endothelium-dependent relaxations in canine veins differentially.

Acetylcholine↗
PubMed1991

Hypoxic contraction of canine coronary arteries: role of endothelium and cGMP.

The effect of severe hypoxia in quiescent or contracted (prostaglandin F2 alpha) canine coronary artery rings with and without endothelium was studied. Hypoxia induced an initial transient relaxation followed by a sustained contraction. The hypoxic contraction in quiescent rings was comparable in rings with and without endothelium. The facilitation of the contraction to prostaglandin F2 alpha was more pronounced in rings with endothelium. Increasing the level of contractions by augmenting the contraction of prostaglandin F2 alpha potentiated the hypoxic contraction in rings with endothelium only. Methylene blue, LY 83583, and nitro-L-arginine reversed the hypoxic facilitation in contracted rings into relaxation, whereas M&B 22948 augmented it. In quiescent coronary preparations, methylene blue reversed the hypoxic contraction into relaxation in preparations with and without endothelium, whereas nitro-L-arginine had the same effect in vessels with endothelium only. SIN-1, nitroglycerin, and dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) unmasked hypoxic facilitation in rings without endothelium. This was not observed with isoproterenol. The measurement of the level of cGMP revealed an increased level in rings with endothelium compared with those without endothelium under control oxygenation. This difference disappeared during hypoxia due to a decrease of cGMP content in vessels with endothelium. The results suggest that a moderate increase of the cGMP level in vascular smooth muscle is a prerequisite for the occurrence of hypoxia-induced facilitation in contracted canine coronary arteries.

Animals↗
PubMed1993

Endothelium dependence of effects of high PCO2 on agonist-induced contractility of rat aorta.

To investigate the modulation of CO2 and endothelium of vascular contraction induced by various agonists, we studied the influence of high PCO2 (PCO2 = 91 mmHg, pH = 6.99) on the response of endothelium-intact and -rubbed rat aortic preparations to KCl, phenylephrine (PE), and human-porcine endothelin-1 (ET-1). Response of endothelium-intact aortic preparations to KCl was not influenced by both high PCO2 and the pH-matched acidotic solution (7.00) with normal PCO2, whereas that of endothelium-rubbed preparations was attenuated solely by high PCO2. With cyclooxygenase inhibitors or a thromboxane A2 receptor antagonist, high PCO2 attenuated the respose of both preparations to KCl. The dose-response curve of endothelium-intact and -rubbed preparations to PE was shifted to the right by both high PCO2 and the pH-matched acidotic solution with normal PCO2. The maximal response of endothelium-intact preparation to PE was attenuated by high PCO2. Indomethacin augmented the inhibitory action of high PCO2 on the PE-induced contraction. Contractile responses of endothelium-intact and -rubbed preparations to ET-1 were not influenced by high PCO2. With indomethacin, high PCO2 also had no influence on the ET-1-induced contraction of endothelium-intact preparations. Endothelium modified the high PCO2 effects on the time-contraction responses to the three agonists. CO2 and endothelium may variously modify the responses of rat aorta to different agonists. Cyclooxygenase-related eicosanoid(s) may be involved in the effects of high PCO2 on the response of rat aortic smooth muscle cells to KCl and PE.

Animals↗
PubMed1993

Modulation of cerebral arterial tone by endothelium-derived relaxing factor.

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

Animals↗
PubMed1999

Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation.

BACKGROUND: Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS: Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS: In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

Acetylcholine↗
PubMed2003

A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR.

A modified bioassay system was designed to demonstrate the diffusible nature of endothelium-derived contracting factor(s) released by acetylcholine in the aorta of spontaneously hypertensive rat. In "sandwich"-like layered preparation, isometric tension was recorded from a bioassay strip (without endothelium) in the presence of N(G)-nitro-L-arginine and tetrahydrobiopterin to selectively potentiate endothelium-dependent contractions. A donor strip (with or without endothelium) was stitched on the bioassay tissue so that it did not directly contribute to the recorded contractions. Acetylcholine induced contractions that occurred only when the donor strip was with endothelium. Superoxide dismutase did not affect but catalase and the combination of superoxide dismutase plus catalase significantly decreased the endothelium-dependent contraction. The contractions in the layered preparations were abolished when the donor strip with endothelium was treated previously with valeryl salicylate, an irreversible cyclooxygenase-1 inhibitor, but remained unaffected when the bioassay strip was treated with the compound. Previous treatment of the bioassay strip alone with S 18886 abolished the contractile response, whereas treatment of the donor strip with endothelium by the selective TP receptor antagonist only produced a moderate inhibition. These results indicate that in the aorta of spontaneously hypertensive rats, endothelium-dependent contractions to acetylcholine involve a diffusible substance(s) released by the endothelium. The production of this contracting factor(s) requires the activation of endothelial cyclooxygenase-1, and its action the activation of TP receptors on the vascular smooth muscle cells.

Acetylcholine↗
PubMed1986

Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat.

To study the mechanism of decreased endothelium-dependent relaxations in spontaneously hypertensive rats (SHR), rings of thoracic aorta with and without endothelium were taken from age-matched male SHR and normotensive Wistar-Kyoto rats (WKY) and suspended for isometric tension recording. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR but not in those from WKY. These contractions were inhibited by atropine but not by hexamethonium and were prevented by inhibitors of phospholipase A2 or cyclooxygenase but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandin D2, E1, E2, and F2 alpha caused concentration-dependent contractions in rings without endothelium from both SHR and WKY; the responses to the highest concentration (10(-5) M) of the individual prostaglandins were comparable in both strains. Endothelium-dependent relaxations evoked by high but not by low concentrations of acetylcholine were significantly depressed in SHR as compared with those in WKY (p less than 0.05). Indomethacin normalized endothelium-dependent relaxations in SHR. Thus, acetylcholine can activate muscarinic receptors that evoke endothelium-dependent contractions in the aorta of SHR but not in that of WKY. The contraction probably is mediated by a cyclooxygenase product(s) other than prostacyclin or thromboxane A2. The reduced endothelium-dependent relaxations to acetylcholine in the SHR probably are not due to a decreased release of endothelium-derived relaxing factor(s) but to the simultaneous release of endothelium-derived contracting substance(s).

Acetylcholine↗
PubMed1989

Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.

The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2 = 42 +/- 1 mm Hg) in the presence of indomethacin (2.8 x 10(-5) M). This moderate degree of hypoxia inhibited (p less than 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p less than 0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than in endothelium-denuded vessels (0.70 +/- 0.12 vs. 0.09 +/- 0.03 g, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗